The factors responsible for the development of an immune response to spermatozoa in some individuals but not in others, have not been eludicated. Recent data have led to the hypothesis, to be tested in the present application, that suppressor T lymphocytes present in semen and/or the ability of seminal fluid to activate suppressor cells aid in minimizing an immune response to spermatozoa in males and females. Sera and peripheral blood mononuclear cells (PBMN) will be obtained from 100 male and female partners with primary infertility and 35 male and female partners of fertile marriages. Semen will be obtained from all men. All sera and semen will be tested for sperm and seminal fluid-reactive antibodies. The numbers of suppressor and helper T lymphocytes in the ejaculates will be quantitated with monoclonal antibodies. The ability of seminal lymphocytes to block in vitro proliferation and immunoglobulin production by the semen donor's PBMN, by those of his spouse or of control PBMN, will be determined. Similarly, the induction of suppressor cell activity in PBMN of husband and wife following incubation with husband or control seminal fluid will be assessed. To ascertain the origin of the seminal fluid component which induces suppressor cell activity, pre- and post-vasovasostomy seminal fluids from 30 men, as well as epididymal fluid obtained at the time of surgery, will be incubated with PBMN and tested for their effect on lymphocyte proliferation and immunoglobulin production. To determine the cell type(s) required for seminal fluid activation of suppressor cells, macrophages, T lymphocytes and B lymphocytes will be isolated, incubated alone or in various combinations with seminal fluid and tested for immunosuppressive properties.